The major translational goals of molecular diagnostic and minimal residual disease (MRD) studies in the CALGB Leukemia Correlative Science Committee (LCSC) are to identify new prognostic groups and to utilize this information to adapt therapy to improve treatment outcome. We propose to consolidate all molecular diagnostic and MRD monitoring studies into a comprehensive "Molecular Detection and Monitoring Core" that will provide high quality data to Leukemia Committee clinical trials and to other LCSC projects and cores. The work will be performed in three disease-specific laboratories: Dr. Stock's laboratory (University of Chicago) for ALL and CML; Dr. Slack's (Roswell Park) laboratory for APL; and Dr. Gribben's (Dana Farber) laboratory for CLL. Several goals are proposed for Project 5. First, we will continue to utilize Real-time PCR technology for the prospective molecular detection of specific disease subsets and evaluation of MRD, correlating these findings with response to novel therapies as they are tested in the next generation of CALGB leukemia trials in ALL, APL, CML, and CLL. We propose that assessment of response using quantitative MRD monitoring as a surrogate endpoint provides unique clinical insights that will be particularly relevant as we perform the first generation of molecularly targeted CALGB leukemia trials described below in detail. A second goal of Project 5 is to validate the use of quantitative MRD monitoring as an independent prognostic marker of outcome for patients with acute and chronic leukemia. Prospective MRD evaluation of large, uniformly treated patient cohorts is essential for identification and validation of a "threshold" level of MRD that may distinguish patients at high (or low) risk of relapse. We also propose, for the first time in CALGB Leukemia studies, to utilize MRD monitoring to adapt and individualize post-remission therapy. A fourth goal of this Project is closely linked to Project 3, Gene Profiling Studies in Leukemia. As new molecular "signatures" characterizing novel disease subsets are identified by gene profiling studies in Project 3, we will evaluate expression levels of new "molecular signature" genes in ALL, AML and CLL, using Real-time reverse transcriptase (RT)-PCR methodology. The correlation of gene expression using Real-time RT-PCR with microarray findings will be useful for validating these data and will provide important new diagnostic and prognostic information about new molecular genetic subsets that may be used to adapt therapy in future CALGB treatment trials.